Phorbol esters down-regulate protein kinase C in rat brain cerebral cortical slices.
The effect of phorbol esters on cyclic AMP production in rat cerebral cortical slices was studied using a prelabelling technique to measure cyclic nucleotide accumulation. Cholera toxin-stimulated cyclic AMP accumulation was enhanced approximately 2-fold by phorbol 12-myristate, 13-acetate (PMA) which alone had no effect on cyclic AMP production. The augmentation by PMA was maximal within the first hour of incubation, decreasing progressively thereafter. Protein kinase C activity was decreased 80-90% during a 3 hr exposure to PMA, as was 3H-phorbol 12,13-dibutyrate binding. Both phosphatidyl serine and arachidonic acid were found to enhance protein kinase C activity in a concentration-dependent manner, an effect that was attenuated by prolonged incubation of the brain tissue with PMA. The results indicate that exposure of brain slices to phorbol esters causes a down-regulation of rat brain protein kinase C, and that this modification corresponds with a decrease in the ability of PMA to augment cyclic AMP production, suggesting a functional relationship between the two systems in rat brain.
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Related Subject Headings
- Tetradecanoylphorbol Acetate
- Rats
- Protein Kinase C
- Phosphatidylserines
- Phorbol Esters
- Phorbol 12,13-Dibutyrate
- In Vitro Techniques
- Cyclic AMP
- Cholera Toxin
- Cerebral Cortex
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tetradecanoylphorbol Acetate
- Rats
- Protein Kinase C
- Phosphatidylserines
- Phorbol Esters
- Phorbol 12,13-Dibutyrate
- In Vitro Techniques
- Cyclic AMP
- Cholera Toxin
- Cerebral Cortex